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Biomedical subjects

D A Gabriel

Publications and source records attributed to D A Gabriel.

At least 37 records · Page 2Linked to original sources
PubMed1998

Practice effects on the timing and magnitude of antagonist activity during ballistic elbow flexion to a target.

This study examined changes in antagonist timing and magnitude in response to ballistic elbow flexion practice. Seventeen men performed 400 ballistic elbow flexion trials to a target in the horizontal plane over 4 days of testing. A potentiometer and microswitch system at the elbow axis of rotation of a manipulandum recorded angular displacement and movement onset. Surface electrodes (Beckman Ag/AgCl) monitored the triceps brachii lateral head, and the electromyographic (EMG) signals were bandpassed between 20 and 300 Hz. The antagonist EMG burst was divided in two: early low-level activity (ANT1), and the large portion of the burst which occurs near target achievement (ANT2). Movement time decreased from 178 ms on the first test day to 136 ms on the last session. As practice improved the speed of limb movement, onset of the first component (ANT1) remained unchanged, while the second component (ANT2) started earlier. The magnitude of both portions of the antagonist burst increased from the first to last test day, but the change in ANT2 relative to ANT1 was more pronounced. These findings are used to explain discrepant observations in the literature for the temporal measure.

Adaptation, Physiological↗
PubMed1997

The physical exchange of factor VIII (FVIII) between von Willebrand factor and activated platelets and the effect of the FVIII B-domain on platelet binding.

Normal hemostasis proceeds through the assembly of coagulant complexes on a lipid surface derived from activated platelets. The activation complex assembly is governed by multiple factors including the binding constants (Kd) of the coagulant factors for the lipid surface. The formation of the tenase complex requires delivery of factor VIII (FVIII) to the activated lipid surface by von Willebrand factor (vWF). Using electrophoretic quasi-elastic light scattering (ELS), we have examined the interaction of FVIII in the presence and absence of vWF with both resting and activated gel-filtered human platelets. Resting platelets do not bind FVIII. Platelets activated by thrombin, epinephrine, or SFLLRN, but not ADP or collagen, bind unactivated FVIII if vWF is not present. In the absence of vWF, unactivated FVIII binds to activated platelets with a Kd of 10.4 nM. B-domain deleted FVIII binds to activated platelets with a Kd of 5.1 nM. Thrombin -activated FVIII (FVIIIa) binds to activated platelets with a Kd of 1.7 nM. The activation of FVIII while bound to the platelet surface can be monitored as a function of time. In the presence of vWF, binding of unactivated FVIII to activated platelets was inhibited, but not the binding of FVIIIa. Displacement of bound unactivated FVIII from the platelet surface occurs when vWF is added to the FVIII-platelet complex. The binding of FVIII to activated platelets is affected by the B-domain, the state of FVIII activation, and the presence of soluble vWF and proceeds as a multistep process. FVIII binding by activated platelets is not affected by platelet gpIIb/IIIa or by platelet vWF.

Binding Sites↗
PubMed1997

Shoulder and elbow muscle activity in goal-directed arm movements.

This research examined the electromyographic (EMG) activity of shoulder and elbow muscles during reaching movements of the upper limb. Subjects performed goal-directed arm movements in the horizontal plane. Movements which varied in amplitude, speed, and direction were performed in different sections of the workspace. EMG activity was recorded from the pectoralis major, posterior deltoid, biceps brachii short head, brachioradialis, triceps brachii long head, and triceps brachii lateral head; motion recordings were obtained with an optoelectric system. The analysis focused on the magnitude and timing of opposing muscle groups at the shoulder and elbow joints. For hand movements within any given direction of the workspace direction, kinematic manipulations changed agonist and antagonist EMG magnitude and intermuscle timing in a manner consistent with previous single-joint findings. To produce reaching movements in different directions and areas of the workspace, shoulder and elbow agonist EMG magnitude increased for those hand motions which required higher angular velocities, while the timing between opposing muscle groups at each joint was invariant.

Arm↗
PubMed1997

Reversal of antagonists: effect of elbow extension strength and endurance.

OBJECTIVE: To evaluate the reversal of elbow antagonists designed to facilitate the extensors relative to agonist-only contractions of the extensors, while using a protocol previously demonstrated to result in an increase in strength through motor learning. DESIGN: Two-group convenience sample composed of healthy subjects. SETTING: Clinic research laboratory. SUBJECTS: Twenty-eight healthy women without a history of upper extremity injury or neurologic disorder. MEASUREMENTS: Elbow extension strength and endurance were measured during maximal effort isometric reversal of the elbow antagonists (experimental group) and elbow extension only (control group) resistance exercise. Biceps brachii short head (BBS), triceps brachii lateral head (TLAT), and triceps brachii long head (TLNG) electromyographic (EMG) activity was measured concurrently. RESULTS: There were no significant differences between groups for either elbow extension strength, BBS, TLAT, or TLNG EMG activity. The experimental and control groups exhibited a significant linear (p < .01) and quadratic (p < .01) increase in baseline strength of 5.2N.m (30.5%). EMG activity from each muscle group increased linearly (p < .01) across all test sessions. Similar results were observed for elbow extension strength and biceps and triceps EMG activity during fatigue testing. CONCLUSIONS: The reversal of antagonists technique was not superior to agonist-only resistance exercise, nor did it interfere with the acquisition of muscular strength or endurance through motor learning.

Adult↗
PubMed1997

Differences between contrast media in the inhibition of platelet activation by specific platelet agonists.

RATIONALE AND OBJECTIVES: The authors evaluated the ability of three x-ray contrast agents--a nonionic monomeric agent (iohexol), a nonionic dimeric agent (iodixanol), and an ionic dimeric agent (ioxaglate)--to either directly activate platelets or inhibit a platelet agonist from activating platelets. METHODS: Fluorescence spectroscopy was used to detect the effect of contrast media on platelet activation. In this method, the platelet is first exposed to a fluorescent probe, which is de-esterified and trapped to Fluo-3 within the platelet. In the presence of calcium, the fluorescence emission from Fluo-3 is increased 80-fold. Thus, the increase in the free platelet calcium associated with platelet activation can be used to indicate platelet activation. RESULTS: None of the agents were shown to directly activate platelets. However, wide differences in the ability of contrast media to inhibit platelet activation by a specific agonist were observed. Activation of platelets by epinephrine or arachidonic acid was not affected by any of the three contrast media studied. All three agents partially inhibited collagen activation of platelets, with ioxaglate the more potent inhibitor. Ioxaglate was the only agent to inhibit thrombin activation of platelets. Inhibition of adenosine diphosphate platelet activation was more extensive with ioxaglate than with iodixanol; iohexol produced no inhibition at all. CONCLUSION: Direct activation of platelets by contrast media was not observed. Of greater importance is the finding that ionic contrast media, but not nonionic contrast media, inhibit thrombin activation of platelets by binding to the anion-binding exosite I, thus preventing thrombin from binding to and activating the platelet.

Arachidonic Acid↗
PubMed1996

Variable influence of heparin and contrast agents on platelet function as assessed by the in vitro bleeding time.

Both heparin and contrast agents have anticoagulant effects which are well-documented but their effects on platelets are not well-characterized. The purpose of the present study was to evaluate the sequential effects of heparin and then a contrast agent on platelet function during an angiographic procedure. Blood samples from 54 patients were obtained at baseline, after a 5000 unit bolus of heparin and after administration of a contrast agent (iohexol, n = 30: diatrizoate, n = 24) during angiography. The in vitro bleeding time (IVBT) was determined on nonanticoagulated whole blood using a hollow fiber device under physiological flow conditions. Mean IVBT at baseline was 3.6 +/- 2.7 minutes and increased to 17.0 +/- 12.3 minutes after heparin (p < 0.01). After heparin, 44.5% of the patients still had a normal IVBT (< 9.0 minutes), 11% of the patients had a moderately increased IVBT and the remaining patients had a large increase in their IVBT. When contrast was given (167 +/- 52 mls) following heparin, mean IVBT was higher in those who received diatrizoate (23.3 +/- 9.4 minutes) compared with iohexol (15.0 +/- 10.9 minutes, p < 0.05). However, 15 patients (28%) continued to have a normal IVBT after contrast and of these 80% had received iohexol.

Aged↗
PubMed1996

Transient intermediates in the thrombin activation of fibrinogen. Evidence for only the desAA species.

The structure of a fibrin gel depends on the nature of the fibrinogen activation products produced by thrombin and the physical condition under which assembly occurs. Two different structures of the intermediate fibrin protofibril have been proposed, the production of which requires different extents of fibrinopeptide A (FpA) cleavage from fibrinogen. The fibrin activation intermediates must be stable since time is required for the intermediates to diffuse to growing protofibrils. The classic Hall-Slayter model requires cleavage of both FpAs to form a desAA intermediate. The Hunziker model requires cleavage of only one FpA to form an AdesA intermediate. Electrophoretic quasi elastic light scattering has been used to show the time-dependent production of the relevant fibrinogen activation intermediates that includes desAA but not AdesA.

Fibrin↗
PubMed1996

Effect of iodixanol on in vitro bleeding time.

RATIONALE AND OBJECTIVES: Both monomeric and dimeric ionic radio contrast media (CM) have been shown to be more anticoagulant than nonionic monomeric CM. Iodixanol is a relatively new nonionic dimeric contrast medium. We investigated whether the dimeric structure of iodixanol would produce the same level of anticoagulation that has been observed using nonionic monomeric CM. METHODS: We used a global screening device that operates under physiologic flow conditions to monitor the effects of iodixanol on in vitro bleeding time (IVBT). This flow dynamic technique perfuses nonanticoagulated whole blood through a hollow fiber device. A leak in the fiber is created by a precision needle, and the resulting pressure fluctuations within the fiber are monitored to examine the ability of the hemostatic system to close the leak by forming a stable platelet plug. RESULTS: In 20 donors, iodixanol (25% CM/blood, v/v) was shown to lengthen the mean IVBT (18.74 min) compared with the normal blood mean IVBT (4.24 min). CONCLUSION: The addition of dimeric iodixanol to normal blood affects the IVBT in the same manner as nonionic monomeric CM (ioversol, iopamidol, and iohexol).

Anticoagulants↗
PubMed1995

A prospective study of treatment of acquired (autoimmune) factor VIII inhibitors with high-dose intravenous gammaglobulin.

A decrease in inhibitor titer has been reported in some patients with acquired factor VIII inhibitors treated with intravenous gammaglobulin (IGIV). We have conducted a prospective, multicenter study of high-dose IGIV in treatment of this disorder to determine efficacy. Nineteen patients received induction therapy with IGIV, 1,000 mg/kg x 2 consecutive days or 400 mg/kg x 5 consecutive days, followed by maintenance doses at intervals as clinically indicated. A > or = 25% reduction in inhibitor titer was observed in 8 of 16 assessable patients, six of whom met the criteria for response. A rapid decline in inhibitor titer over 3 to 4 days was observed in two patients, but in four additional responding patients--two of whom received repetitive maintenance doses of IGIV--the decline was more gradual, with final nadirs being reached several weeks to many months after treatment. The inhibitor disappeared in three patients with low-level inhibitors, less than 1 Bethesda unit (BU). Concomitant therapy with prednisone may have contributed to the response in two of the patients but was not a factor in four patients; the response rate is, therefore, estimated to be between 25% and 37.5%. These results confirm the beneficial effect of IGIV in treatment of some patients with acquired autoimmune factor VIII inhibitors.

Adult↗
PubMed1995

Intramolecular domain-domain interactions and intermolecular self-association in bovine prothrombin. A potentiometric and laser light-scattering study.

The interaction of bovine prothrombin with Ca2+ and Mg2+ ions was investigated by following H+ release as a function of metal ion concentration at pH 6 and pH 7.4 at high and low ionic strength. Prothrombin Ca2+ and Mg2+ binding is characterized by high- and low-affinity sites. M2+ binding at these sites is associated with intramolecular conformational changes and also with intermolecular self-association. The pH dependence of H+ release by M2+ is bell shaped and consistent with controlling pKa values of 4.8 and 6.5. At pH 6 and low ionic strength, both Ca2+ and Mg2+ titrations following H+ release clearly show independent low- and high-affinity binding sites. Laser light scattering reveals that at pH 7.4 and low ionic strength, and at pH 6.0 and high ionic strength, the prothrombin molecular weight is between 73 and 98 kD. At pH 7.4 and high ionic strength, prothrombin is monomeric in the absence of metal ions, but appears to dimerize in the presence of M2+. At pH 6.0 and low ionic strength prothrombin exists as a dimer in the absence of metal ions and is tetrameric in the presence of Ca2+ and remains dimeric in the presence of Mg2+. These results and those for metal ion-dependent H+ release indicate that H+ release occurs concomitantly with association processes involving prothrombin.

Animals↗
PubMed1995

Effect of contrast media on in vitro bleeding time: assessment by a hollow fiber instrument.

RATIONALE AND OBJECTIVES: We used a global screening device that operates under physiologic flow conditions to monitor the effects of ionic and nonionic contrast media (CM) on hemostasis. METHODS: This flow dynamic technique perfuses unanticoagulated whole blood through a hollow fiber. A leak in the fiber is created by a precision needle, and the resulting pressure fluctuations within the fiber are monitored to examine the ability of the hemostatic system to close the leak by forming a stable platelet plug. RESULTS: Both ionic and nonionic CM (25% CM/blood, v/v) were shown to lengthen the mean in vitro bleeding times (IVBTs) compared with normal blood. Ionic CM (ioxaglate and diatrizoate) consistently produced IVBTs longer than 30 min. The nonionic CM iopamidol, iohexol, and ioversol gave mean IVBTs of 16.43, 17.63, and 19.84 min, respectively. CONCLUSION: Of the three nonionic CM tested, iopamidol had the greatest probability (31%) of producing an IVBT in the normal range, with probabilities of 5% and 7% for iohexol and ioversol, respectively. Thus, iopamidol offered the least anticoagulant effect among the ionic and nonionic CM we studied.

Bleeding Time↗
PubMed1995

A flow dynamic technique used to assess global haemostasis.

Global haemostasis was assessed on blood from patients with established blood clotting abnormalities using a hollow fibre flow device. The instrument monitors pressure changes across a polyethylene fibre through which non-anticoagulated whole blood is perfused. This method of analysis is significant because it (1) minimizes or eliminates common problems associated with routine clinical evaluations, such as sample dilution, completion time, and anticoagulant artifacts, (2) rapidly (under 90 min) and accurately calculates in vitro bleeding time (IVBT) and whole blood clotting time (WBCT), (3) presents a reliable means of distinguishing coagulation defects from platelet dysfunction, and (4) reduces the need for a series of screening tests to a single test that requires a small amount of non-anticoagulated whole blood. Using this technology, global haemostasis of normal volunteers was studied using blood samples spiked with PPACK and prostacyclin. Blood from patients with acquired factor VIII deficiency and Glanzmann's thrombasthenia and from those receiving Coumadin therapy were also studied. The hollow fibre device detailed haemostatic abnormalities of both congenital and therapeutic conditions.

Bleeding Time↗
PubMed1993

Electrophoretic light scattering studies on the interaction of fibrinogen with resting and activated human platelets.

The interaction of the platelet surface with agonist or adhesive molecules can modify the platelet surface charge and thus its electrophoretic mobility. Electrophoretic quasi elastic light scattering (ELS) is a technique that permits the rapid and accurate determination of electrophoretic mobility of platelets. ELS was used to study changes in the platelet electrophoretic mobility induced by platelet activation and by fibrinogen binding. The platelet electrophoretic mobility decreases from -2 (mu-cm)/(V-s) to -0.5 (mu-cm)/(V-s) when the platelet is activated with either 1 microM ADP, 10 microM epinephrine or 0.5 NIH U/ml alpha-thrombin. Aspirin inhibits the ADP induced platelet activation and surface charge reduction. Thrombin overcomes the aspirin inhibition indication that the platelet surface charge reduction is associated with platelet activation. The magnitude of the decrease in the platelet electrophoretic mobility varies with the platelet donor and the extent of platelet activation. Platelet activation enhances the fibrinogen induced surface charge reduction, which is consistent with fibrinogen binding. Thus, ELS is shown to be a sensitive means to directly assess platelet activation and ligand binding.

Aspirin↗
PubMed1992

The effect of fibrin structure on fibrinolysis.

Fibrin structure contributes to the regulation of the fibrinolytic rate. As the fibrin fiber size is decreased, the fibrinolytic rate also decreases. Fibrin structure was altered by either changing the ratio of thrombin to fibrinogen, i.e. altering the assembly rate or by adding a fibrin assembly inhibitor, iopamidol. Changes in the fibrinolytic rate were followed by measuring the time dependence of the decrease in the fiber mass/length ratio during fibrinolysis. A measure of the overall fibrinolytic rate was determined from the decrease in the mass/length ratio versus time. An 8-fold reduction in the fibrinolytic rate was seen on decreasing the mass/length ratio from 2.7 x 10(12) daltons/cm to 0.5 x 10(12) daltons/cm. It is shown that thin fibrin fibers have a decreased rate of conversion of plasminogen to plasmin by tissue plasminogen activator and that thin fibrin fibers are lysed more slowly than thick fibrin fibers.

Amino Acid Sequence↗
PubMed1991

Platelet and fibrin modification by radiographic contrast media.

The effect of the radiographic contrast agents, iopamidol and diatrizoate, on fibrin assembly and structure as well as platelet surface charge was studied. Increasing the iopamidol concentration from 0 to 4.5 mM prolongs the fibrin gelation time from 20 to 105 seconds (an anticoagulant effect) and reduces the fibrin fiber mass/length ratio from 3.2 x 10(12) to 0.5 x 10(12) Da/cm (i.e., produces very thin fibrin fibers). Ultraviolet difference spectroscopy of fibrinogen showed both a 15-nm shift in the ultraviolet difference maximum for iopamidol (suggesting binding) and a perturbation of the aromatic amino acid side chain region for fibrinogen (suggesting a conformational change in fibrinogen) as the concentration of iopamidol was increased from 0 to 9 mg/ml. Binding of iopamidol to fibrinogen was also shown by affinity chromatography using a Sepharose-fibrinogen column. Electrophoretic quasi elastic light scattering was used to show platelet interaction with iopamidol as reflected in a reduction in the platelet electrophoretic mobility from 2.0 to 0.5 (microns-cm)/(V-sec) as the concentration of iopamidol was increased from 0 to 4.5 mM. In addition, the ionic radiopaque contrast agent, Renografin, was also studied and found to inhibit fibrin monomer assembly. Although iopamidol is not shown to be thrombogenic, iopamidol does appear to reduce platelet surface charge, bind fibrinogen, and modify fibrin clot structure.

Blood Platelets↗
PubMed1990

Thrombotic and cardiovascular complications related to nonionic contrast media during cardiac catheterization: analysis of 8,517 patients.

The incidence of major complications associated with nonionic contrast media has not been defined in a large study. Accordingly, cardiovascular complications, especially thrombotic events, were prospectively evaluated in 8,517 consecutive patients undergoing diagnostic cardiac catheterization with either iopamidol (n = 6,293) or iohexol (n = 2,224). Thrombotic events were defined as coronary embolus, coronary occlusion, transient ischemic attack or stroke occurring at the time of catheterization. Thrombotic events occurred in 15 patients (0.18%). Coronary thrombus or embolus occurred in 7 patients, a thromboembolus from the ventricular catheter occurred in 1 patients and transient ischemic attack or stroke occurred in 7 patients. Six of 15 patients with thrombotic events were premedicated with heparin. Thrombotic events were unusual in that they tended to occur in clusters within short time intervals. On 1 occasion, a thrombus was observed in the catheter tip before embolization. Other cardiovascular complications were similarly low with an incidence of ventricular tachycardia/fibrillation of 0.1%, profound bradycardia of 0.2% and prolonged angina of 0.3%. There were 2 deaths unrelated to thrombotic events. Although the clinical thrombotic events associated with nonionic contrast have an unusual temporal clustering and may result in major complications, the overall incidence (0.18%) of these thrombotic complications with nonionic contrast agents is quite similar to that reported with ionic contrast media.

Aged↗
PubMed1989

Effect of homo poly(L-amino acids) on fibrin assembly: role of charge and molecular weight.

Positively charged molecules such as protamine, leukocyte cationic protein, and the carboxyl terminus of platelet factor 4 have been shown to increase fibrin fiber thickness. Synthetic homo poly(L-amino acids) were used to explore the role of charge and molecular weight of cationic molecules on fibrin assembly. The effects of poly(L-lysine) (PLL), poly(L-glutamic acid) (PLG), poly(L-aspartic acid) (PLA), poly(L-histidine) (PLH), and poly(L-arginine) (PLArg) on the assembly and structure of fibrin gels were studied by using light-scattering techniques. At a PLG (Mr 60,000) concentration of 80 micrograms/mL and a PLA (Mr 20,000) concentration of 64 microgram/mL, neither of these negatively charged polymers produced a detectable change in either fibrin assembly kinetics or final structure. Positively charged PLArg (16 micrograms/mL) caused a 30% increase in fibrin fiber mass/length ratio without calcium. In contrast, PLH (16 micrograms/mL), also positively charged, had no effect in the absence of CaCl2 but produced a 40% increase in fiber mass/length ratio with 5 mM CaCl2. At concentrations as low as 1 microgram/mL, positively charged PLL increased the initial fibrin assembly kinetics and led to larger fiber mass/length ratio. The impact on fibrin mass/length ratio was equivalent for three different molecular weight preparations of PLL (Mr 25,000, 90,000, and 240,000). The lack of a molecular weight effect on fiber thickness and the low polymer concentrations required to produce the perturbation argue against an excluded volume effect as the mechanism by which lateral fiber growth is augmented. Mechanisms by which poly(L-amino acids) may perturb fibrin assembly are discussed.

Fibrin↗